Fetal anomalies
Gene: ENPP1

ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1)
EnsemblGeneIds (GRCh38): ENSG00000197594
EnsemblGeneIds (GRCh37): ENSG00000197594
OMIM: 173335, Gene2Phenotype
ENPP1 is in 16 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.

Panel Version: 1.836

Comment on list classification: Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'Q4_21_rating' tag)
Created: 2 Nov 2021, 4:56 p.m. | Last Modified: 2 Nov 2021, 4:56 p.m.

Panel Version: 1.764

Created: 2 Nov 2021, 4:56 p.m.
Last Modified: 2 Nov 2021, 4:56 p.m.
Panel version: 1.836

Rhiannon Mellis (Great Ormond Street Hospital)

Green List (high evidence)

This gene and phenotype were re-reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.

Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).

Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.

Details of review:
Phenotype is hypophosphataemic rickets / arterial calcification of infancy. Previously reviewed as not fetally relevant as not felt to be detectable in utero. New evidence considered from Aggarwal et al 2020 (PMID: 31742715), who report a fetus with homozygous missense variants presenting with hydrops and on post-mortem had macrocephaly and arterial calcification found on histopathology. Consanguineous couple with previous affected pregnancy.

Further reports of ENPP1 mutations with arterial calcification of infancy presenting as hydrops in PMID: 19521093 and PMID: 19813208. Additionally, ABCC6 is the other known GACI gene and is already Green on fetal anomalies panel so suggest ENPP1 should be the same for consistency.
Created: 29 Oct 2021, 1:37 p.m. | Last Modified: 29 Oct 2021, 1:37 p.m.

Panel Version: 1.749

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Generalised arterial calcification of infancy (GACI)

Publications

Created: 29 Oct 2021, 1:37 p.m.
Last Modified: 29 Oct 2021, 1:37 p.m.
Panel version: 1.749

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: Not detectable in utero. Action taken: Demoted ENPP1 gene rating from Green to Red.
Created: 24 Mar 2019, 4:30 p.m.

DDG2P rating in original PAGE list: Confirmed for HYPOPHOSPHATEMIC RICKETS, AUTOSOMAL RECESSIVE, 2 and Confirmed for ARTERIAL CALCIFICATION, GENERALIZED, OF INFANCY, 1.
Created: 11 Dec 2018, 9:04 a.m.

Created: 11 Dec 2018, 9:04 a.m.

Panel version: 0.134

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
PAGE DD-Gene2Phenotype

Phenotypes

Arterial calcification, generalized, of infancy, 1, OMIM:208000

OMIM

173335

Clinvar variants

Variants in ENPP1

Penetrance

None

Publications

Panels with this gene